PSC 833 (valspadar) is a non-immunosuppressive and non-nephrotoxic cyclosporin analogue which is a potent inhibitor of the multidrug resistance transporter, P-glycoprotein. This protocol is of interest because of the activity of paclitaxel and doxorubicin in breast, ovarian and lung cancers. In this Phase I study, we are assessing the effect of PSC 833 on the pharmacokinetics and pharmacodynamics of doxorubicin and paclitaxel, with the goal of defining: a) a maximally tolerated dose (MTD) of doxorubicin with paclitaxel; b) maximally tolerated doses for doxorubicin and paclitaxel in conjunction with PSC 833; and c) the maximally tolerated doses of doxorubicin, paclitaxel, and PSC, utilizing G-CSF support. Patients initially receive doxorubicin and paclitaxel and are being enrolled in cohorts of three to ten patients per cohort. Detailed pharmacokinetics for doxorubicin, doxorubicinol, and paclitaxel are being performed. We anticipate that PSC 833 will significantly increase the area under the curve and the half-life of both doxorubicin and paclitaxel. This study is ongoing and should be completed during the current grant year.